The feud between these two men was forged in 2008 and has festered ever since, first when Mourinho was in charge at Inter Milan and then when he was Barcelona coach Guardiola’s biggest rival in Spain at Real Madrid.
Now it is heading for the Premier League as United counter the 45-year-old Catalan’s move to City by installing his old nemesis across town. The two most successful coaches in world football are going head to head, just over four miles apart.
Following the monotony of United’s football under Louis van Gaal and the grey presence of Manuel Pellegrini at City, things are about to get very interesting again.
The rivals will meet for the first time in their new jobs at the Bird’s Nest Stadium in Beijing on July 25.
It is a peculiar setting for a Manchester derby, yet somehow appropriate given the global interest in the Premier League and what is sure to be a captivating battle between two vastly contrasting characters.
Mourinho, the pragmatist, schemer and master of the dark arts, will be charged with making sense of the muddle left by his old boss Van Gaal.
Guardiola, the reserved advocate of beautiful football, has the challenge of taking City to the next level.
Neither will be short of the funds to succeed in their task. Watching them try to do it will be pure box office.
It has the potential to dwarf the rivalry between these clubs in the late 60s and early 70s - when City were in their pomp and United had just won the European Cup - and more recently when the noisy neighbours first got under Sir Alex Ferguson’s skin.
The fallout from a mischievous billboard welcoming Carlos Tevez to Manchester when he moved from United to City will be nothing compared to the sparks Mourinho and Guardiola can produce.
What people do not always realise is that the two men used to be quite close.
There is an image of them embracing warmly after Barcelona won the UEFA Cup-Winners’ Cup in Rotterdam in 1997 when Guardiola was a player and Mourinho a more humble assistant to Bobby Robson.
However, their relationship soured when Barca gambled in 2008 by appointing the inexperienced Guardiola to replace Frank Rijkaard as coach and overlooked a bitter Mourinho who had set his heart on the job, even considering approaching Pep to be his No 2.
The Portuguese turned against his old club. He went to Inter Milan instead and delighted in beating Barcelona in the semi-final of the Champions League in 2010.
It is understood that a cardboard cut-out of Mourinho racing across the Nou Camp pitch to celebrate that night, moments before he was intercepted by goalkeeper Victor Valdes, stood proudly in his office at Real Madrid’s training base when he returned to Spain in the summer to renew his rivalry with Guardiola.
It turned increasingly toxic as Mourinho seized every opportunity to goad the Barcelona coach, who finally snapped in April 2011 before another Champions League semi-final - one of four clasico meetings between the two clubs in the space of three weeks.
‘In this room (Real Madrid’s press room), he is the chief, the f***ing man and I can’t compete with him,’ said Guardiola.
‘If Barcelona want someone who competes with that, then they should look for another manager. But we, as a person and an institution, don’t do that.
‘We worked together for four years. He knows me, I know him and that’s all. If this matters more than our relationship, then that’s up to him. It leaves a bad taste in your mouth when someone you had a relationship with does what he has done.’
Some thought Guardiola had lost the plot but his players later gave him a standing ovation and duly won the game - one of his seven victories over Mourinho, who has won only three of their 16 encounters.
When the Spanish Super Cup clash between the two clubs at the start of the following season descended into a brawl, Mourinho was involved in one of his most shameful episodes as he crept up behind Guardiola’s assistant Tito Vilanova and gouged his right eye.
The draining intensity of their rivalry was said to be one of the reasons why Guardiola wanted to take a sabbatical after he left Barcelona at the end of that season.
When he agreed to leave Bayern Munich and join City last December, the same month Chelsea sacked Mourinho, he was no doubt hoping to avoid his old foe in the Premier League.
Indeed, there was said to be surprise in the Guardiola camp that United have turned to Mourinho in light of the sorry situation he left behind at Stamford Bridge.
Now they are both heading for Manchester and the pistols are drawn again.
Original source: Pep v Jose: Manchester derby the new El Clasico